ArticleNature communications2021
rRNA biogenesis regulates mouse 2C-like state by 3D structure reorganization of peri-nucleolar heterochromatin.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 66 citations in OpenAlex.
- Decoding Biomolecular Phase Separation: From Physiological Roles to Pathological Mechanisms and Therapeutic Biomaterials Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Article
- Culture medium modulates nucleolar architecture and disrupts ribosomal RNA levels in preimplantation mouse embryos.The Journal of reproduction and development · 2026Article
- Alterations in chromatin organization promote totipotent-like features in a DPPA2/DUX-dependent manner.The EMBO journal · 2026Article
- Nuclear envelope-dependent heterochromatin positioning gates the timing of nucleolar assembly in the early embryo.bioRxiv : the preprint server for biology · 2026Article
- A nucleolar stress gene signature enables quantitative scoring across multi-omics contexts.Communications biology · 2026Article
- Shugoshin 2A stabilizes heterochromatin complexes to suppress the 2-cell-like state in embryonic stem cells.Stem cell reports · 2026Article
- Nucleoli-localized KANSL2 as an epigenetic regulator of ribosome biogenesis in glioblastoma cells.Communications biology · 2026Article
- Dynamic Landscape of Alternative Splicing During Early Embryogenesis of the Rhesus Monkey.International journal of molecular sciences · 2026Article
- Nucleolar expansion: A biomolecular condensate mortality timer.Geromedicine · 2026Article
- Exit from totipotency in mammals: an epigenetic perspective.Frontiers in cell and developmental biology · 2026Review
- How Early-Life Programming During Embryogenesis Imprints Cellular Memory.International journal of molecular sciences · 2025Review
- The TDG protein environment connects active DNA demethylation with chromatin and RNA biology.Cellular and molecular life sciences : CMLS · 2025Article
- Sex-specific expression and function of TRIM28 during mouse primordial germ differentiation.iScience · 2025Article
- A molecular census to elucidate the demixing mechanism of membraneless organelles.Genome biology · 2025Article
- Hypertranscription of rDNA Responsible for Nucleolar Remodelling is a Doorman for Acquiring Pluripotency.Cell proliferation · 2025Article
- Ints7 deficiency activates DNA damage response to elicit resurgence of endogenous retrovirus MERVL and anastasis of embryonic stem cells.Nucleic acids research · 2025Article
- USP17L promotes the 2-cell-like program through deubiquitination of H2AK119ub1 and ZSCAN4.Nature communications · 2025Article
- Positive coactivator PC4 shows dynamic nucleolar distribution required for rDNA transcription and protein synthesis.Cell communication and signaling : CCS · 2025Article
- Nat10 maintains the homeostasis of pluripotent and 2-cell-like states in mouse embryonic stem cells through mRNA cytidine acetylation.Nucleic acids research · 2025Article
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. However, its role in regulating stem cell fate remains unclear. Here, we present evidence that nucleolar stress induced by interfering rRNA biogenesis can drive the 2-cell stage embryo-like (2C-like) program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells. Mechanistically, nucleolar integrity maintains normal liquid-liquid phase separation (LLPS) of the nucleolus and the formation of peri-nucleolar heterochromatin (PNH). Upon defects in rRNA biogenesis, the natural state of nucleolus LLPS is disrupted, causing dissociation of the NCL/TRIM28 complex from PNH and changes in epigenetic state and reorganization of the 3D structure of PNH, which leads to release of Dux, a 2C program transcription factor, from PNH to activate a 2C-like program. Correspondingly, embryos with rRNA biogenesis defect are unable to develop from 2-cell (2C) to 4-cell embryos, with delayed repression of 2C/ERV genes and a transcriptome skewed toward earlier cleavage embryo signatures. Our results highlight that rRNA-mediated nucleolar integrity and 3D structure reshaping of the PNH compartment regulates the fate transition of mES cells to 2C-like cells, and that rRNA biogenesis is a critical regulator during the 2-cell to 4-cell transition of murine pre-implantation embryo development.
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